TY - JOUR
T1 - Polymorphisms in the angiogenesis-related genes EFNB2, MMP2 and JAG1 are associated with survival of colorectal cancer patients
AU - Scherer, Dominique
AU - Deutelmoser, Heike
AU - Balavarca, Yesilda
AU - Toth, Reka
AU - Habermann, Nina
AU - Buck, Katharina
AU - Kap, Elisabeth Johanna
AU - Botma, Akke
AU - Seibold, Petra
AU - Jansen, Lina
AU - Bermejo, Justo Lorenzo
AU - Weigl, Korbinian
AU - Benner, Axel
AU - Hoffmeister, Michael
AU - Ulrich, Alexis
AU - Brenner, Hermann
AU - Burwinkel, Barbara
AU - Chang-Claude, Jenny
AU - Ulrich, Cornelia M.
N1 - Funding Information:
Funding: D. Scherer was supported by an Olympia Morata fellowship of the Medical Faculty, University of Heidelberg and the German Federal Ministry of Education and Research (01KT1510). The DACHS study was supported by grants from the German Research Council (Deutsche Forschungsgemeinschaft, grant numbers BR 1704/6–1, BR 1704/6–3, BR 1704/6–4, BR 1704/6–6, CH 117/1–1, HO 5117/2–1, HE 5998/2–1, KL 2354/3–1, RO 2270/8–1, and BR 1704/17–1), and the German Federal Ministry of Education and Research (grant numbers 01KH0404, 01ER0814, 01ER0815, 01ER1505A and 01ER1505B). CM Ulrich was supported by R01 CA189184, U01 CA206110 and R01 CA 207371.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - An individual’s inherited genetic variation may contribute to the ‘angiogenic switch’, which is essential for blood supply and tumor growth of microscopic and macroscopic tumors. Polymorphisms in angiogenesis-related genes potentially predispose to colorectal cancer (CRC) or affect the survival of CRC patients. We investigated the association of 392 single nucleotide polymorphisms (SNPs) in 33 angiogenesis-related genes with CRC risk and survival of CRC patients in 1754 CRC cases and 1781 healthy controls within DACHS (Darmkrebs: Chancen der Verhütung durch Screening), a German population-based case-control study. Odds ratios and 95% confidence intervals (CI) were estimated from unconditional logistic regression to test for genetic associations with CRC risk. The Cox proportional hazard model was used to estimate hazard ratios (HR) and 95% CIs for survival. Multiple testing was adjusted for by a false discovery rate. No variant was associated with CRC risk. Variants in EFNB2, MMP2 and JAG1 were significantly associated with overall survival. The association of the EFNB2 tagging SNP rs9520090 (p < 0.0001) was confirmed in two validation datasets (p-values: 0.01 and 0.05). The associations of the tagging SNPs rs6040062 in JAG1 (p-value 0.0003) and rs2241145 in MMP2 (p-value 0.0005) showed the same direction of association with overall survival in the first and second validation sets, respectively, although they did not reach significance (p-values: 0.09 and 0.25, respectively). EFNB2, MMP2 and JAG1 are known for their functional role in angiogenesis and the present study points to novel evidence for the impact of angiogenesis-related genetic variants on the CRC outcome.
AB - An individual’s inherited genetic variation may contribute to the ‘angiogenic switch’, which is essential for blood supply and tumor growth of microscopic and macroscopic tumors. Polymorphisms in angiogenesis-related genes potentially predispose to colorectal cancer (CRC) or affect the survival of CRC patients. We investigated the association of 392 single nucleotide polymorphisms (SNPs) in 33 angiogenesis-related genes with CRC risk and survival of CRC patients in 1754 CRC cases and 1781 healthy controls within DACHS (Darmkrebs: Chancen der Verhütung durch Screening), a German population-based case-control study. Odds ratios and 95% confidence intervals (CI) were estimated from unconditional logistic regression to test for genetic associations with CRC risk. The Cox proportional hazard model was used to estimate hazard ratios (HR) and 95% CIs for survival. Multiple testing was adjusted for by a false discovery rate. No variant was associated with CRC risk. Variants in EFNB2, MMP2 and JAG1 were significantly associated with overall survival. The association of the EFNB2 tagging SNP rs9520090 (p < 0.0001) was confirmed in two validation datasets (p-values: 0.01 and 0.05). The associations of the tagging SNPs rs6040062 in JAG1 (p-value 0.0003) and rs2241145 in MMP2 (p-value 0.0005) showed the same direction of association with overall survival in the first and second validation sets, respectively, although they did not reach significance (p-values: 0.09 and 0.25, respectively). EFNB2, MMP2 and JAG1 are known for their functional role in angiogenesis and the present study points to novel evidence for the impact of angiogenesis-related genetic variants on the CRC outcome.
KW - Angiogenesis
KW - Colorectal cancer
KW - Single nucleotide polymorphism
KW - Survival
UR - http://www.scopus.com/inward/record.url?scp=85088977066&partnerID=8YFLogxK
U2 - 10.3390/ijms21155395
DO - 10.3390/ijms21155395
M3 - Article
C2 - 32751332
AN - SCOPUS:85088977066
SN - 1661-6596
VL - 21
SP - 1
EP - 15
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 15
M1 - 5395
ER -